Pharmacotherapy of Pompe disease

Abstract

Introduction: Pompe disease (PD) is a metabolic myopathy caused by the deficiency of acid alfa-glycosidase (GAA). Several therapeutic approaches have been proposed to treat this disorder. These include enzyme replacement therapy (ERT) with recombinant human GAA (the only approved treatment for PD), small molecule-based therapies, gene therapy, substrate reduction, and approaches directed toward the manipulation of secondarily affected cellular pathways.

Areas covered: The efficacy of ERT, the potential for clinical translation of the other approaches listed previously, and the advantages and the limitations of each of them are evaluated in this review.

Expert opinion: Each of the therapeutic approaches shows advantages and limitations. ERT was successful in treating cardiac involvement, but has limited distribution to target tissues, requires life-long repeated infusions, and is highly expensive. Pharmacological chaperone therapy has advantages compared with ERT in terms of biodistribution and oral intake. However, chaperones are effective only on a limited number of mutations. Gene therapy is an attractive strategy and is now being translated into clinical trials, but needs further evaluation. Other approaches are still in an early phase of research and development. The combination of various therapies should be carefully evaluated and may translate into personalized therapeutic protocols.

Keywords::

• enzyme replacement therapy
• gene therapy
• pharmacological chaperone therapy
• Pompe disease

Notes

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